Abstract / Summary
Rationale: Schizophrenia is a serious mental health condition that can cause long-term disability and major disruption to daily life. People living with schizophrenia may experience psychosis, causing frightening and distressing experiences. At times, this distress may lead to aggressive or violent behaviour towards themselves or others. On such occasions, medications used for the management of aggression and agitation in psychiatric settings must have a rapid onset of action, low frequency of administration and exhibit a minimal adverse-effect profile. Zuclopenthixol acetate is reported to have these properties.
Objectives: To evaluate the clinical effectiveness of zuclopenthixol acetate in the management of acute behavioural disturbance in people with acute schizophrenia and similar major mental illnesses, compared with other pharmacological agents used for the treatment of similar clinical presentations.
Search methods: We searched the Cochrane Schizophrenia Study-Based Register of Randomised Controlled Trials, CENTRAL and MEDLINE, supplemented by citation searching and contacting study authors. The date of the last search was 8 September 2025.
Eligibility criteria: Randomised controlled trials (RCTs) involving participants with major mental illnesses that compared zuclopenthixol acetate with standard pharmacological treatments were included, with predefined exclusion criteria applied.
Outcomes: Our outcomes were tranquillisation, sedation (measured between 15 minutes and 48 hours), global state (including the need for additional medications), behaviour, mental state and adverse effects (evaluated up to seven days). These outcomes were also used to compare lower doses of zuclopenthixol acetate (25 mg to 50 mg per injection) with higher doses (50 mg to 100 mg per injection).
Risk of bias: We used the Cochrane risk of bias tool (RoB 1).
Synthesis methods: Data extraction and cross-checking were performed independently by the review authors, and the risk of bias in the included studies was systematically assessed. We synthesised results for each outcome using meta-analysis where possible. Review Manager and the GRADE profiler were used for data synthesis and evaluation of the certainty of evidence.
Included studies: We included 11 studies with 714 participants. All studies were RCTs and investigated the effect of intramuscular zuclopenthixol acetate. The risk of bias was variable: two studies reported adequate random sequence generation, one confirmed allocation concealment, four reported participant blinding and five reported assessor blinding. Outcomes were clearly reported in three studies, but selective reporting was identified in 10 of 11 included studies. Overall, the certainty of evidence ranged from moderate to very low.